The overall objective of this research project is to develop specific information about the molecular basis for the mutagenic activity of cyclopenta(cd)pyrene (CPP), a polycyclic aromatic hydrocarbon without a bay-region which is widely distributed in the environment. Our studies of CPP metabolism, mutagenicity, and toxicity will permit us to evaluate both the relative contributions of the various enzymes involved in PAH metabolism and the contributions of specific DNA lesions and repair processes to the biological effects of CPP. No non-bay region PAH has been studied in great depth and the knowledge we seek about CPP could contribute much to our fundamental understanding of structure-activity relationships for PAH both at the level of metabolism and at the level of DNA. Our studies of CPP metabolism by purified rabbit liver cytochrome P-450, by rat liver microsomes, and by mammalian cells in culture-including mouse embryo fibroblast C3H 10T1/2 cells, and normal human and rat epithelial cells derived from esophagus, skin, and vagina--will provide fundamental information about such aspects of PAH metabolism as the factors contributing to a substrate's regio-specific oxidation by cytochrome P-450 enzymes, the role of specific enzymes (conjugating enzymes and epoxide hydrase) in detoxifying highly reactive arene oxides like CPP-3,4-oxide, and the ability of epithelial cells--the cells which give rise to 80% of human cancers--to metabolish PAH. Our studies on the formation and repair of CPP induced DNA damage in mammalian cells and in bacterial cells with genetically determined differences affecting either their capacity to repair DNA lesions or their susceptibility to killing and mutagenesis by alkylating agents will contribute to our understanding of the roles of specific DNA adducts and DNA repair pathways in mutagenesis and toxicity.